The subject matter of the invention is a nephro-urological medicament which is especially suitable for combatting phosphate renal calculi.
In epidemiological studies of recent years it has been shown that an average of 4% of the adult population suffers once or more often in the course of life from renal calculi (kidneystones). Renal calculi are borderline cases of biomineralization. They are caused by a number of pathologicoanatomic, metabolical and physiochemical factors. The causes of renal calculi formation also determine their composition. By physiochemical methods of examination, such as infrared spectroscopy and X-ray diffraction, it is possible to perform a precise, quantitative analysis of renal calculi.
A large amount--about 15 to 20%--of the renal calculus consists of various phosphates. A summary of the phosphates most frequently occurring in the renal calculus is given below.
Chemical names, chemical formula, and mineralogical names of the most important phosphate kidneystones:
______________________________________ Mineral- ogical Chemical name Formula name ______________________________________ Calcium hydrogen CaHPO.sub.4 2H.sub.2 O Brushite phosphate Tricalcium phosphate Ca.sub.3 (PO.sub.4).sub.2 Whitlockite Hydroxycalcium Ca.sub.10 (PO.sub.4).sub.6 (OH).sub.2 Hydro- phosphate xylapa- tite Carbonate apatite Ca.sub.10 (PO.sub.4 CO.sub.3 OH).sub.6 (OH).sub.2 Dahllite Magnesium ammonium MgNH.sub.4 PO.sub.4.6H.sub.2 O Struvite phosphate ______________________________________
A deciding factor in the formation of phosphate calculi is the pH of the urine. The overwhelming number of phosphate calculi form in an alkaline environment. Apatite, carbonate apatite and struvite crystallize, for example, at urine pH levels above 7.0. Brushite, however, crystallizes at urine pH levels of 6.8 to 7.0.
The formation of phosphate renal calculi is based on a variety of causes. Some causes are urinary infections by germs producing urease, which alkalinize the urine by the cleavage of urea; the result is a supersaturation of magnesium ammonium phosphate, calcium phosphate and monoammonium urate in the urine, followed by crystalluria and the subsequent formation of kidneystones like the above-named: struvite, carbonate apatite and monoammonium urate. In this development, aggravating factors are normally present, such as an excessively low urine volume, a deficiency of citrate or inhibitors, and an excessively high concentration of calcium and phosphate in the urine.
Another cause of the formation of calcium phosphate concretions is metabolical disturbances, such as renal tubulary acidosis, which likewise leads to an elevation of the pH in the urine; the incomplete form of renal tubulary acidosis can be compensated by acidification of the urine.
Furthermore, in addition to the altered calcium and phosphate excretion, e.g., under the conditions of primary hyperparathyroidism, the urine pH is an aggravating factor in the formation of phosphate stones. Accordingly, a lowering of the pH may here again be necessary.
The therapeutic object in cases of phosphate stone diathesis, namely the acidification of the urine, should always be accomplished with the lowest possible burden on the metabolism. Consequently, those medicaments are to be favored which in low dosage produce a high acidifying action.
To combat phosphate calculi, L-methionone, NH.sub.4 Cl, acidolpepsin, and ascorbic acid have been used as urinary acidifying agents. In some cases, very high daily doses of these drugs must be applied if a sufficient urinary acidification is to be achieved. Also due to the necessary high absorption, however, the organism is at the same time subjected to a high metabolical stress. This is true especially of the liver metabolism, and can lead to alteration of the blood and urine analysis.
The object of the invention was therefore a preparation for urinary acidification which can be administered in sufficient quantity without excessive stress on the organism, especially on the liver metabolism.